Disease-responsive Synthetic Cell Therapy

Objective

This project aims to develop programmable, disease-responsive synthetic cells capable of sensing and adapting to pathological microenvironments—specifically hypoxia and acidity—by synthesizing and releasing therapeutic proteins on demand. Synthetic Cell Therapy, a novel class of precision medicine, will combine the adaptability of engineered living cell therapies with the precision and controllability of synthetic drug delivery systems. By leveraging the safety, modularity, and programmability of bottom-up synthetic biology, the proposed work addresses key limitations of current therapeutics, including immune rejection and uncontrolled behavior (engineered cell therapy), poor targeting and premature drug release (synthetic drug delivery system). Two complementary strategies will be explored: (1) gene circuit–mediated therapeutic synthesis and release, and (2) physicochemical multi-stage drug release. WP1 will develop stimuli-responsive gene circuits for in situ transcription–translation of therapeutic proteins and pore-formers within microfluidic-generated synthetic cells, enabling real-time, stimuli-triggered therapeutic action. WP2 will engineer multi-compartmental synthetic cells with membrane lipids responsive to hypoxia and acidity, enabling graded, multi-stage release based on disease severity. Together, these approaches offer lifelike adaptive therapeutic behavior with spatial, temporal, and dosage control. This interdisciplinary proposal integrates synthetic biology, microfluidics, biomembrane engineering, and pharmaceutical sciences, aligning with MSCA priorities in excellence, interdisciplinary and frontier research. The project addresses unmet medical needs in cancer and neurodegeneration and advances next-generation, safe, and intelligent precision medicine platforms, contributing to the Horizon Europe goals of fostering innovation, strengthening Europe's research competitiveness, and improving healthcare outcomes.